It is described that an α-glucosidase inhibitors inhibits the α-glucosidase localized at the fine villies in the small intestine, and controls the rapid increase in blood glucose after meal and next increase in blood insulin level (Diabetes Medicine, 10, 688, 1993). Since they suppresses/slow down the metabolism of dietary carbohydrates in human and animals, and exhibit an inhibitory effect of blood glucose increases, they are found effective in improving hyperglycemic conditions as well as various diseases induced by hyperglycemia such as obesity and diabetes.
Glucosidases are also found involved in the transformation of normal cells to cancer cells and in tumor cell invasion and migration. It has also been observed that level of serum glucosidases are elevated in many patients with different tumors and are thought to be involved in the degradation of the extra cellular matrix in tumor cell invasion (Cancer Matastasis Rev. 4, 81, 1985). Therefore, the use of glucosidase inhibitors to prevent abberations during glycoprotein processing and to inhibit catabolic glycosidases is being actively pursued as therapeutic strategy for cancer. (Phytochemistry 56, 265, 2001).
Furthermore, many animal viruses contain an outer envelop, which is composed of one or more viral glycoprotein. These glycoproteins are often essential proteins in that they are required in the viral life cycle, either in viron assembly and secretion and/or infectivity. As the processing of these glycoproteins occurs through the cellular machinery, inhibitors of processing α-glucosidases have been shown to decrease the infectivity of broad range of human pathogenic viruses (FEBS letters 430, 17, 1998 and Phytochemistry 56, 265, 2001).
Similarly, α-glucosidase inhibitors have also been found to restore the immune response of immunocompromized experimental animals (Chem. Pharm. Bull. 39, 2807, 1991). Therefore α-glucosidase inhibitors are also extensively been worked out for their exploitation as immunostimulants.
There are several α-glucosidase inhibitors known in the literature and are under clinical practice (Phytochemistry 56, 265, 2001). However, it is still felt that when more of the α-glucosidase inhibitor compounds of natural origin with varied skeleton become available commercially, there is sure to be even wider range of potentially valuable activities found than shown to date.
Plants continue to be used world wide for the treatment of disease and novel drug entities continue to be developed through research in to their constituents. Despite the massive arsenal of clinical agents developed by the pharmaceutical industry there has been aversion by many members of the public. This public aversion further paved the way for use of herbal medicines. Therefore, herbal remedies have proved to be popular as alternative treatment of disease. Due to this powerful Green Wave sweeping all over the world, the demand for herbal drug has increased several folds.
This current trend has accelerated the scientific investigations and evaluation of folklore and traditional medicinal plants used for the treatment of variety of ailments world over. These efforts have led to the isolation and identification of several novel chemical entities. These chemical entities were also found to possess variety of biological activities of multiple therapeutic importances.
Dichrostachys cinerea is a medicinal plant used in the traditional Indian system of medicine. It is widely advocated in diuretic, lithotriptic, anodyne, and inflammatory conditions. Further, it is found useful in arthralgia, elephantiasis, dyspepsia, diarrhea, nephropathy etc (Indian Medicinal Plants, Vol. 2 p. 330, 1995). Dichrostachys cinerea is also found useful in opthalmia, rheumatism, urinary calculi and renal troubles (Wealth of India Vol. 3 p. 56, 1952) and has been reported to possess protease inhibitory (CA, 90, 118086u), antifungal (Ind. J. Plant. Physiol, 29, 278–80, 1986), and antibacterial activity (Fitoterapia, 59, 57–62, 1988.).
In this invention, (−)-mesquitol is isolated from the methanolic extract of stem of Dichrostachys cinerea in very good yield (1.5% yield from the dried plant material). (−)-mesquitol is an optical isomer of (+)-mesquitol which was previously isolated from Prosopis grandulosa in 0.01% yield (J. Chem. Soc. Perkin. Trans I, 1737, 1986). However, this isomer of mesquitol has not been tested for any biological activity to the best of our search.
Despite the wide use of Dichrostachys cinerea in Indian traditional system of medicinal practice, efforts of isolating and identifying biologically active molecules are still lacking. As molecules isolated from traditional medicinal plants have shown multiple biological activities of therapeutic importance, we investigated Dichrostachys cinerea and observed that (−)-mesquitol is present in D. cinerea in significant yield and possess potent α-glucosidase inhibitory activity, which may find broad therapeutic application. We also made efforts to prepare analogues of the compound (−)-mesquitol in order to enhance the α-glucosidase inhibitory activity.